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Systemic inflammation and vascular function were not affected by immediate airway challenges involving bronchoconstriction (methacholine) or inflammation and bronchoconstriction (mannitol) in a recent clinical trial.

Asthma is a persistent respiratory disorder characterized by repetitive instances of inflammation in the airways, leading to the constriction of the bronchial tubes and the manifestation of symptoms such as wheezing, dyspnea, and a sensation of pressure in the chest. Recent studies have brought attention to an increased susceptibility to cardiovascular illness in persons diagnosed with asthma, with the likelihood of developing such conditions rising in correlation with the severity of asthma symptoms.

The inhalation of mannitol has been observed to stimulate mast cells located in the airways, resulting in the release of inflammatory mediators and cytokines. This phenomenon bears resemblance to the mechanisms observed during episodes of asthma exacerbation. Additionally, a correlation exists between asthma exacerbations and an elevated susceptibility to cardiovascular events. 

This randomized case-control trial, published in the journal PloS One, assessed the mannitol airway challenge, which is recognized as an effective method for identifying airway hypersensitivity.

Participant Characteristics

The study involved 26 participants diagnosed with asthma and 25 individuals without asthma who served as controls. The characteristics of the participants were well matched concerning variables such as height and weight. A greater percentage of participants with asthma exhibited allergies, and their pre-bronchodilator forced expiratory volume in one second (FEV1) and FEV1/forced vital capacity (FVC) ratios were significantly reduced compared to those of the control group.

Assessing FEV1 Responses Across Airway Challenges

The investigation evaluated the FEV1 reactions to placebo, mannitol, and methacholine. The control group had no alterations in FEV1 in response to all trials. On the other hand, it was shown that individuals diagnosed with asthma exhibited noteworthy decreases in FEV1, particularly when subjected to challenges involving mannitol and methacholine. It is worth mentioning that a significant proportion of subjects demonstrated a favorable airway reaction to both mannitol and methacholine.

Consistent Systemic Inflammatory Marker Levels

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The investigation analyzed indicators of systemic inflammation, such as C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor (TNF), both prior to and following each stimulus. No statistically significant differences were observed in the levels of systemic inflammatory markers in controls and individuals with asthma.

Pulse Wave Velocity Increase Following Mannitol Challenge

The assessment included the evaluation of vascular function by measures such as flow-mediated dilation (FMD), microvascular function (VHR), and arterial stiffness, expressed as pulse wave velocity (PWV). The results of the study indicate that there was an observed elevation in PWV among participants with asthma after undergoing the mannitol challenge as opposed to the placebo challenge.

Inflammatory and Vascular Responses Unaltered in Favorable Challenge Outcomes

A further analysis was conducted to examine the vascular and inflammatory responses in people who demonstrated favorable challenge findings, which were defined by notable reductions in FEV1. The analysis findings revealed that the levels of CRP, TNF, IL-6, FMD, and VHR were not affected by the type of challenge administered.

Moore, L. E., Brotto, A. R., Fuhr, D. P., Rosychuk, R. J., Wong, E., Bhutani, M., & Stickland, M. K. (2023). Impact of airway challenges on cardiovascular risk in asthma – a randomized controlled trial. PloS one, 18(7), e0288623. https://doi.org/10.1371/journal.pone.0288623